This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Simulating the dynamics of protein folding has been a challenge for decades. Moreover, since protein folding is an iconic problem with connections to many fields, the ability to tackle protein folding will have a broad impact across diverse fields. Over the last 5 years, there has been dramatic progress in the field with Markov State Model (MSM) approaches, yielding simulations of protein folding in all-atom detail, on the millisecond timescale. Here, we propose to synergistically fuse MSM approaches and the uniquely powerful capabilities of ANTON in order to go beyond what either method could do on its own: we propose to run a single, long trajectory on ANTON and follow up with milliseconds of aggregate MD using Folding@home. We proposed to simulate the folding of BBL in explicit solvent. BBL is a prime target due to its wealth of experimental data, its potential role as a downhill (barrier free) folder, but yet still controversial due to potentially conflicting experimental data. If successful, the result would be a fully detailed model for how this protein folds, potentially shedding light on the seemingly contradictory experiments as well as elucidating more directly the chemical nature of the mutants which lead to downhill folding. Most significantly, this work would demonstrate how to efficiently and synergistically combine HPC resources and distributed computing, with implications for many other molecular simulation problems as well.